Makindo Medical Notes

⚠️ Amphotericin B binds to fungal ergosterol but also interacts with human cholesterol → explaining its major toxicities, especially nephrotoxicity. 💊 Liposomal amphotericin B (Ambisome® or equivalent generic) is the preferred formulation in the UK: far less nephrotoxic and better tolerated than conventional amphotericin B deoxycholate. 👨‍⚕️ Use only under specialist guidance, with strict dosing and monitoring protocols.

📖 About

• Polyene antifungal antibiotic produced by Streptomyces nodosus.
• Reserved for progressive, potentially life-threatening systemic fungal infections.
• Administration and monitoring require senior specialist involvement (Infectious Diseases, Haematology, or ICU).

⚙️ Mode of Action

• Binds preferentially to ergosterol in fungal cell membranes.
• Forms transmembrane pores → leakage of intracellular K⁺ and Mg²⁺ → cell death.
• Partial affinity for mammalian cholesterol explains renal tubular and infusion toxicities.

🩺 Indications

• Severe or disseminated candidiasis (including candidaemia).
• Cryptococcal meningitis (often combined with flucytosine).
• Invasive aspergillosis and other mould infections (e.g. mucormycosis, fusariosis).
• Visceral leishmaniasis (specialist tropical use).
• Empirical antifungal therapy in high-risk neutropenic fever (specialist setting).

⚠️ Adverse Effects

• Infusion-related reactions: fever, rigors, hypotension, nausea — slow infusion and pre-medication reduce risk.
• Nephrotoxicity: tubular injury → ↑creatinine, ↓GFR (less with liposomal formulations).
• Electrolyte loss: hypokalaemia, hypomagnesaemia, hyponatraemia → risk of arrhythmia.
• Haematological: normocytic anaemia (suppression of erythropoietin).
• Occasional hepatotoxicity or allergic reactions.

🔄 Drug Interactions

• ↑ Nephrotoxicity with ciclosporin, tacrolimus, aminoglycosides, or NSAIDs.
• Hypokalaemia increases risk of digoxin toxicity and potentiates QT prolongation.
• Concomitant diuretics or corticosteroids worsen electrolyte loss.

💉 Dose (Refer to BNF / Product Datasheet)

🧪 Monitoring

• Renal function: U&Es and creatinine at baseline, then ≥twice weekly (daily if unwell).
• Electrolytes: K⁺, Mg²⁺, Na⁺ — replace promptly if low.
• LFTs and FBC: monitor for hepatotoxicity and anaemia.
• Observe during infusion for rigors, anaphylaxis, or arrhythmia.
• Ensure pre-hydration with normal saline before and during therapy.

📚 References

• BNF: Amphotericin B
• UKHSA / Public Health England: Invasive Fungal Infection Guidelines
• MHRA Product Information: Ambisome® (liposomal amphotericin B)